Conventional therapeutic treatments for infectious diseases are becoming increasingly ineffective with the emergence of resistant mutant strains of infectious agents. Antimicrobial agents have been widely described for the treatment of bacterial infections. Many improvements in the administration of antimicrobial agents have been suggested for treating drug resistant mutants; for enhancing therapeutic activity in the treatment of specific infections; and, for lessening the toxicity of individual drugs. These improvements include the development of synthetic analogues and administration of combinations of antibiotics. A number of delivery systems have also been developed for gradually releasing antimicrobial agents in vivo. One approach to obtaining prolonged release of an antimicrobial agent has been to encapsulate the agent in a vesicle known as a liposome. Liposomes are typically micellular particles which are spherical in form and which are derived from a lipid which forms a layered membrane. Typically liposomes are prepared from a phospholipid such as distearoyl phosphatidyl-choline or lecithin. A liposome may be a simple shell (a unilamellar vesicle) or it may form in multiple layers (multilamellar vesicle). However, liposome preparations have a number of disadvantages including the wide heterogeneity in size distribution, the number of lamellae, and the low trapping efficiency of the aqueous space which restricts the ability to encapsulate large molecules. Liposomes are also difficult and costly to produce.
Notwithstanding the advances in antimicrobial agents, new therapeutic agents and delivery vehicles are required particularly for the treatment of infectious diseases caused by resistant mutants and for the treatment of mixed bacterial infections.
Conventional prophylactic treatments for infectious diseases are also becoming increasingly ineffective with the emergence of resistant mutant strains of infectious agents. Vaccines for the prophylaxis of infectious diseases have been developed which incorporate whole attenuated organisms, cell lysates, culture supernatants or extracts of the infectious agents. There has been considerable interest in improving existing vaccines since they typically contain fractions having physical or chemical characteristics which result in toxicity or undesired immune responses.
In order to address these problems attempts are being made to use recombinant DNA techniques to express protective antigens such as lipopolysaccharide from pathogenic bacteria in live, attenuated, carrier strains. These hybrid strains have been demonstrated to be effective vaccine strains since they cannot replicate in vivo, but can still invade and deliver the antigens to host tissue to engender an immune response. However, the use of genetic procedures to transfer foreign genes into attenuated strains has several disadvantages; for example, instability of cloned genes, expression of antibiotic resistance following strain construction, reversion to virulence, accumulation of recombinant antigen in cytoplasm, and poor surface expression for recognition by the immune system. Recombinant vaccines are also costly to make. The construction of a multivalent vaccine is even further complicated due to many variables such as the necessity to develop several constitutive expression systems.